Department of Drugs Industry and Pharmaceutical Management, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureș, Romania.
Department of Organic Chemistry, Semmelweis University, Budapest, Hungary.
Electrophoresis. 2019 Aug;40(15):1897-1903. doi: 10.1002/elps.201800482. Epub 2019 Feb 21.
Pressure-assisted stereospecific capillary electrophoresis method was developed for the determination of enantiomeric purity of the antiparkinsonian agent (R)-rasagiline. The optimized method, 50 mM glycine-HCl buffer pH 2, supplied with 30 mM sulfobutylether-β-cyclodextrin, at 35°C, applying 12 kV in reversed polarity, and -8 mbar pressure (vacuum), short-end injection with -25 mbar × 2 s, was successful for baseline separation of rasagiline enantiomers (R = 3.5 ± 0.1) in a short analysis time. The method was validated according to current guidelines and proved to be reliable, linear, precise and accurate for determination of 0.15% S-enantiomer as chiral impurity in R-rasagiline sample, as well as quantification of the eutomer. Method application was tested on a commercial tablet formulation. Determination of spatial structure of diastereomeric associates was based on H and 2D ROESY NMR, indicating that the aromatic moiety of the molecule can enter the cyclodextrin cavity. NMR titration and molecular modeling revealed that S-rasagiline formed a more stable inclusion complex with sulfobutylether-β-cyclodextrin, than its antipode, which is in agreement with electrophoretic results.
建立了压力辅助立体选择性毛细管电泳法测定抗帕金森病药物（R）-雷沙吉兰的对映体纯度。优化后的方法为 50mM 甘氨酸-HCl 缓冲液 pH 2，添加 30mM 磺丁基醚-β-环糊精，在 35°C 下，施加 12 kV 的反向极性和-8 mbar 的压力（真空），短端进样-25 mbar×2 s，成功实现了雷沙吉兰对映体（R = 3.5±0.1）在短分析时间内的基线分离。该方法根据现行指南进行了验证，结果表明该方法可靠、线性、精确、准确，可用于测定 R-雷沙吉兰样品中 0.15% S-对映体作为手性杂质以及外消旋体的定量。该方法应用于商业片剂制剂进行了测试。对非对映异构体缔合物的空间结构的测定是基于 1 H 和 2D ROESY NMR，表明该分子的芳基部分可以进入环糊精腔。NMR 滴定和分子建模表明，S-雷沙吉兰与磺丁基醚-β-环糊精形成更稳定的包合物，而其对映体则不然，这与电泳结果一致。
